Medical Care

Therapy for ANCA-associated disease consists of a combination of corticosteroids and cyclophosphamide. Treatment with steroids alone results in a 3-fold increase in the risk of relapse compared to combination therapy. The only predictor of renal survival is the serum creatinine value at the time of diagnosis. Therefore, a high index of suspicion is imperative to establish the diagnosis quickly and to institute treatment as soon as possible. Renal failure requiring dialysis is not a contraindication to treatment. Many patients can be removed from dialysis for an extended period (18 mo to 2 y).

The regimen used by the Glomerular Disease Collaborative Network at the University of North Carolina at Chapel Hill
[6, 7] is as follows:

Administer methylprednisolone at 7 mg/kg/d intravenously (not to exceed 1 g) for 3 days, followed by oral prednisone at 1 mg/kg/d (not to exceed 80 mg) for 3 weeks, and then oral prednisone at 2 mg/kg every other day (not to exceed 120 mg) for 3 months. This dose is decreased by 25% every 4 weeks until the patient stops taking prednisone.

Administer cyclophosphamide either intravenously or orally. Intravenous therapy is initially administered at a dose of 0.5 g/m2, and the oral dose is 2 mg/kg. Both are adjusted according to a 2-week leukocyte nadir count (goal 3000-4000/µL). The maximum intravenous dose is 1 g/m2. Oral and intravenous cyclophosphamide appears to be equally efficacious. However, this remains an area of controversy, particularly in the case of granulomatosis with polyangiitis, for which some advocate oral therapy. The advantage to using the intravenous preparation is that the risk of cumulative toxicity is lower because a lower total dose is used.

Another protocol, which has been used widely and with success in Europe, is the substitution of azathioprine for cyclophosphamide after a 3-month induction period. Azathioprine is administered at 2 mg/kg orally in a single daily dose. This is continued for 6-12 months.

Methotrexate has been substituted for cyclophosphamide in the initial treatment of granulomatosis with polyangiitisfor mild disease and has been used for treatment after initial induction therapy with cyclophosphamide in more severe disease.
[8]

Plasmapheresis may be a beneficial addition to therapy for patients who present with severe renal failure (serum creatinine >6 mg/dL) or those who progress despite treatment.

Other medications have been used in an attempt to attain a remission, such as intravenous immunoglobulin, antithymocyte antibody, and humanized monoclonal antibody to CD4 and CD25. None of these therapies has been well studied. They appear in the literature as case reports.

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Consultations

Nephrology consultation should be obtained as early as possible in suspected cases of rapidly progressive glomerulonephritis.

Tables

Contributor Information and Disclosures

Author

James W Lohr, MD Professor, Department of Internal Medicine, Division of Nephrology, Fellowship Program Director, University of Buffalo State University of New York School of Medicine and Biomedical Sciences